Chemiluminescence (CL) has a higher signal-to-noise ratio than fluorescence, but the use of CL to track an enzyme-instructed self-assembly (EISA) process has not been reported. In this work, by coincubation of the hydrogelator precursor Fmoc-Phe-Phe-Tyr(HPO)-OH (1P) and the CL agent AMPPD (2) with alkaline phosphatase (ALP), we employed CL to directly characterize and image the simultaneous EISA process of 1P. Hydrogelation processes of 1P with and without 2 and the CL properties of 2 with and without 1P under ALP catalysis were systematically studied. The results indicated that 2 is an ideal CL indicator for ALP-triggered hydrogelation of 1P. Using an IVIS optical imaging system, we obtained time-course CL images of 2 to track the simultaneous hydrogelation process of 1P in the same solution. We envision that our CL method could be employed to track more biological EISA events in the near future.

Fibroblast activation protein (FAP), a type II transmembrane serine protease, is highly expressed in more than 90% of epithelial tumors and is closely associated with various tumor invasion, metastasis, and prognosis. Using FAP as a target, various FAP inhibitors (FAPIs) have been developed, most of which have nanomolar levels of FAP affinity and high selectivity and are used for positron emission tomography (PET) imaging of different tumors. We have conducted a systematic review of the available data; summarized the biological principles of FAPIs for PET imaging, the synthesis model, and metabolic characteristics of the radiotracer; and compared the respective values of FAPIs and the current mainstream tracer 18F-Fludeoxyglucose (18F-FDG) in the clinical management of tumor and non-tumor lesions. Available research evidence indicates that FAPIs are a molecular imaging tool complementary to 18F-FDG and are expected to be the new molecule of the century with better imaging effects than 18F-FDG in a variety of cancers, including gastrointestinal tumors, liver tumors, breast tumors, and nasopharyngeal carcinoma.

Nanoprobes are advantageous over small molecular probes in sensitivity but most luminescence molecules used to construct nanoprobes often suffer from an aggregation-caused quenching effect. Herein, we rationally designed a small molecular probe Cys(StBu)-Lys(Ru(bpy)32+)-CBT (1) which "smartly" self-assembled into nanoparticles 1-NPs inside cells with non-quenched, persistent phosphorescence. Employing this property, we successfully applied 1 for long-term sensing of biothiol activity in living HepG2 cells and tumors. We envision that, by modifying the amino group with an enzyme substrate, our probe 1 could be further developed for sensing intracellular enzyme activity with non-quenched, persistent phosphorescence.

Lung cancer is the highest incidence and mortality of all cancers around the world. In the present immunotherapy era, an increasing number of immunotherapeutic agents including monoclonal antibody-targeted drugs have been used in the clinical treatment of malignancy, but it still has many limitations. Chimeric antigen receptormodified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have not only been used successfully against hematological tumors, but have also opened up new avenues for immunotherapy of solid tumors, including lung cancer. However, targeting lung cancer-specific antigens using engineered CAR-T cells is complicated by the lack of proper tumor-specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, along with off-target effect, etc. Simultaneously, the clinical application of CAR-T cells remains limited because of many challenges such as tumor lysis syndrome, neurotoxicity syndrome, and cytokine release syndrome. In this review, we outline the basic structure and generation characteristic of CAR-T cells and summarize the common tumorassociated antigens in clinical trials of CAR-T cell therapy for lung cancer, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for the pre-clinical experiments and clinical trials of CAR-T cell therapy in lung cancer. K E Y W O R D S chimeric antigen receptor-modified T cellsimmunotherapylung cancersolid tumortargeting specific antigens